Magnesium is nutritionally important for maintenance of vascular integrity, but is often deficient in fatty, refined modern diets (Seelig et al., Am. J. Clin. Nutr., 27:59-79, 1974). Deleterious vascular effects of magnesium deficiency include cardiac arrhythmias and hypertension (Anderson et al., Can. Med. Assoc. J., 113:199-203, 1975). Magnesium supplements have been shown to reduce such hypertension (Dyckner et al., Brit. Med. J., 286:1847-1849, 1983; Motoyama et al., Hypertension, 113:227-232, 1989; Ryan et al., Ann. Clin. Res., 16:81-88, 1984). intravenous administration of magnesium salts in the treatment of acute myocardial infarction (MI) has been found to decrease the subsequent incidence of arrhythmias and to improve survival. Intravenous magnesium also exerts a therapeutic effect in hypertensive crises, such as that occurring in, for example, intractable arrhythmias. (Ryan et al., 1984; Iseri, Drugs, 16:81-88, 1984; Shechter et al., Arch. Intern, Med., 152:2189-2196, 1992).
Increased extracellular magnesium prevents neuronal calcium overload, is the physiological gating mechanism for the NMDA calcium channel and may reduce calcium influx through other channels or damaged membranes. This calcium-antagonist activity may play a role in the protection of anoxic hippocampal neuron cell cultures (Rothman, Science 220, 536-537, 1983). Hypermagnesemia has also been shown to promote vasodilation of the cerebral arteries.
The efficacy of thrombolytic therapy for acute MI is well established. Intraarterial streptokinase or urokinase has been shown to recanalize thrombotically occluded arteries (Puca, J. Neurosurg. Sci., 37:63-70, 1993; Hacke et al., Stroke, 19:1216-1222). Tissue plasminogen activator (TPA) has also shown promise in promoting urgent recanalization in stroke patients (Brott et al., Stroke, 23:632-640, 1992) . Subsequent to removal of a thrombotic occlusion, adjunctive measures are necessary for optimization of neuron salvage in the ischemic zone and prevention of potentially fatal complications, including reocclusion of the thrombotically cleared artery (Coller, New Engl. J. Med., 322:33-42, 1990).
Cellular calcium overload via influx through voltage-sensitive L-type and NMDA calcium channels is believed to be the main cause of much of the neuronal and vascular dysfunction subsequent to cerebral ischemia (White et al., J. Am. Med. Assoc., 251:1586-1590; Wong et al., Stroke, 21:494-501, 1990). Calcium channel antagonists have been evaluated for promoting neuron salvage and patient survival following cerebral ischemia; however, clinical efforts to assess calcium channel antagonists in acute stroke therapy have so far yielded equivocal, and in some instances disappointing, results (Gelmers et al., New Engl. J. Med., 318:203-207, 1988; Trust Study Group, Lancet, 336:1205-1209, 1990).
Taurine is an amino acid present in high concentrations in excitable and secretory tissue. Its role in cardiac function has received particular attention (Huxtable, Physiol. Rev., 72:101-163, 1992; Schaffer et al., Taurine in Health and Disease, pp. 171-180, 1994). Although taurine can be synthesized endogenously from the amino acid cysteine, in mammals it is derived principally from the diet and is thus considered a "conditionally essential" nutrient. Conventional diets supply 40-400 mg of taurine daily, while vegetarian diets are extremely low in this amino acid (Huxtable, 1992).
The main function of taurine in mammals appears to be the regulation of transmembrane ionic movements, especially the regulation of calcium distribution (Schaffer et al., 1994; Huxtable, 1992; Schaffer et al., Taurine: Functional Neurochemistry, Physiology and Cardiology, pp. 217-225, 1990). Taurine exerts an antihypertensive action in various animal models of hypertension and may also have clinical antihypertensive activity. Taurine also has direct anticonvulsant activity as demonstrated in animal studies and suggested by clinical reports.
Taurine exerts a platelet stabilizing effect both in vitro and, after oral administration, ex vivo (Hayes et al., Am. J. Clin. Nutr., 49:1211-1216, 1989; Atahanov, Arzneim-Forsch/Drug Res., 42:1311-1313, 1992). Taurine can also improve the survival and functional recovery of temporarily hypoxic neurons, while impeding calcium influx (Schurr et al., Life Sci., 40:2059-2066, 1987; Malcangio et al., Psychopharmacology, 98:316-320, 1989). Taurine can reduce the adverse effects of excitotoxic neurotransmitters and drugs, while blocking NMDA-mediated calcium influx. Acute intravenous administration of taurine reduces the incidence of arrhythmias in animals treated with arrhythmogenic agents and multi-gram doses have been shown to be effective in the treatment of ischemic congestive heart failure (Azuma et al., Curr. Ther. Res., 34:543-557, 1983). Thus, increased taurine intake appears to be beneficial to vascular health.
To insure optimal magnesium status, magnesium supplements are frequently advisable. Magnesium supplements are especially important for diabetics, as these individuals typically display reduced intracellular, plasma and bone levels of magnesium. Magnesium oxide is commonly used as a dietary supplement, although the bioavailability of the magnesium in this salt is far from optimal. Soluble magnesium salt complexes with good nutritional availability, including citrate and glycinate, typically are low in magnesium, the majority of the complex consisting of the counteranion which has no nutritional utility.
There is a need in the art for a magnesium-containing composition in which the magnesium is complexed with a counteranion which itself has nutritional and therapeutic/prophylactic utility and would complement the vascular-protective benefits of magnesium. The present invention addresses this need.